A method was worked out for obtaining controlled serial digests of fibrinogen using the pH-shift of buffered solutions to monitor the progress of digestion. This was applied to comparative investigation of the digestion of normal and abnormal fibrinogens. The effect of sodium dodecyl sulfate (SDS) on the esterase activity of trypsin was investigatied. This was necessary for the evaluation of the effectiveness of SDS in inhibiting the enzyme in gel electrophoresis of serial protein digests. SDS has an immediate and a progressive inactivating effect. These are reversed to various extent at high substrate concentrations. The inhibition is not sufficient to assure complete arrest of the digestion in SDS-gel electrophoresis experiments. BIBLIOGRAPHIC REFERENCES: Mihalyi, E., Weinberg, R. M., Towne, D. W. and Friedman, M. E.: Proteolytic fragmentation of fibrinogen. I. Comparison of the fragmentation of human and bovine fibrinogen by trypsin or plasmin. Biochemistry 15: 5372-5381, 1976. Shrager, R. I., Mihalyi, E. and Towne, D. W.: Proteolytic fragmentation of fibrinogen. II. Kinetic modeling of the digestion of human and bovine fibrinogen by plasmin or trypsin. Biochemistry 15: 5382-5386, 1976.